T cells engineered with a T cell receptor against the prostate antigen TARP specifically kill HLA-A2+ prostate and breast cancer cells

Proc Natl Acad Sci U S A. 2012 Sep 25;109(39):15877-81. doi: 10.1073/pnas.1209042109. Epub 2012 Sep 10.

Abstract

To produce genetically engineered T cells directed against prostate and breast cancer cells, we have cloned the T-cell receptor recognizing the HLA-A2-restricted T-cell receptor γ-chain alternate reading-frame protein (TARP)(4-13) epitope. TARP is a protein exclusively expressed in normal prostate epithelium and in adenocarcinomas of the prostate and breast. Peripheral blood T cells transduced with a lentiviral vector encoding the TARP-TCR proliferated well when exposed to peptide-specific stimuli. These cells exerted peptide-specific IFN-γ production and cytotoxic activity. Importantly, HLA-A2(+) prostate and breast cancer cells expressing TARP were also killed, demonstrating that the TARP(4-13) epitope is a physiologically relevant target for T-cell therapy of prostate and breast cancer. In conclusion, we present the cloning of a T cell receptor (TCR) directed against a physiologically relevant HLA-A2 epitope of TARP. To our knowledge this report on engineering of T cells with a TCR directed against an antigen specifically expressed by prostate cells is unique.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Antigens, Neoplasm / biosynthesis
  • Antigens, Neoplasm / genetics
  • Antigens, Neoplasm / immunology*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / immunology
  • Breast Neoplasms / therapy*
  • Cell Engineering*
  • Cell Line, Tumor
  • Female
  • Gene Expression Regulation / immunology
  • HLA-A2 Antigen / genetics
  • HLA-A2 Antigen / immunology*
  • HLA-A2 Antigen / metabolism
  • Humans
  • Immunity, Cellular*
  • Male
  • Nuclear Proteins / biosynthesis
  • Nuclear Proteins / genetics
  • Nuclear Proteins / immunology*
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / immunology
  • Prostatic Neoplasms / therapy*
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Antigen, T-Cell / metabolism
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism

Substances

  • Antigens, Neoplasm
  • HLA-A2 Antigen
  • Nuclear Proteins
  • Receptors, Antigen, T-Cell
  • TARP